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Genetic and environmental influences on the transition from acute to chronic pain Ze’ev Seltzer, DMD Professor of Genetics Canada Senior Research Chair University of Toronto CTR for the Study of Pain Ze’ev Seltzer, DMD Professor of Genetics Canada Senior Research Chair University of Toronto CTR for the Study of Pain

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Conclusions 1. Acute pain sensitivity does not predict levels of chronic pain (3 different chronic pain models, 2 stimulus modalities, 2 species, 2 research groups). 2.Levels of spontaneous chronic pain are not correlated with levels of stimulus-evoked chronic pain. 3.If these results are translatable to humans, genes are ‘syndrome-specific’. Pharmaco-genetic solutions will have to be tailored per syndrome.

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Heritability of chronic pain How much of the variance is accountable by genetics?

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United States Congress declared: 2001-2010: The Decade of Pain Control and Research The Human Genome Project has developed methodological templates that can be transposed immediately to pain genetics. This is the time to: Establish new research teams Support the collections of DNA samples / multicenter approach Finance genome-wide screens using microarray chips (1,000 samples X $ 500/ sample = $ 0.5 million / syndrome) Proposed goal for 2010: First draft listing all major chronic pain genes in humans and mice. Given the right support – this is achievable !

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No Most genes have been fixed throughout evolution (e.g., “Painless” for noxious heat in the fly larva) While many have Single Nucleotide Polymorphisms (SNPs) Only a small fraction are functional, even fewer clinically relevant So how many will have to treated to treat a given pain syndrome? Not known as of yet Guess: ~5 ‘major’ and up to ~15 ‘modifiers’ per syndrome Shall we need to control thousands to treat pain ?

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How many genes would have to be pharmaco-genetically controlled to provide solutions for a pain syndrome?

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Genetic and environmental influences on the transition from acute to chronic pain Ze’ev Seltzer, DMD Professor of Genetics Canada Senior Research Chair University of Toronto CTR for the Study of Pain Ze’ev Seltzer, DMD Professor of Genetics Canada Senior Research Chair University of Toronto CTR for the Study of Pain

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1995 - suffered an accident at work –L. brachial plexus avulsion –L. hand numb and painful –L. hand paralysed at an awkward position The case of Roni A. (male, age 44, contractor)